Natural occurring and induced tumors of rodents may be used to study the possible causes, nature and prevention of human cancer. We have been developing the ACI rat prostate cancer model and have characterized the histogenesis of the prostate preneoplastic and neoplastic lesions. In a long-term lifetime experiment we are studying the effects of 3 retinoids on survival, naturally occurring tumors, and prostate lesions. Interim results suggest that one retinoid prolonged survival of rats. The large granular lymphocyte leukemia in F344 rats is in development as a model for the study of the natural killer cell and its role in tumor immunity. Transplantable LGL tumors with high or low NK activity are utilized to study the potential lineage and activity of LGLs. Experiments are planned to study the role of NK-LGL cells in induced and natural tumor immunity.